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To investigate the scale structure and psychometrics of the EORTC chemotherapy-induced peripheral neuropathy module (QLQ-CIPN20).Using confirmatory factor analyses (CFA), we tested two hypothesized scale structure models of the QLQ-CIPN20 in 473 patients with non-small cell lung cancer, 281 patients with heterogeneous cancer diagnoses, and 500 patients with colorectal cancer. We also modeled the two hypothesized models as bi-factor models. These included a general factor, in addition to the specific domain factors. Additional models were investigated with exploratory factor analysis (EFA). Known groups validity was evaluated where justified.CFA could not confirm the two hypothesized models (Model 1: CFI < 0.926; TLI < 0.914; RMSEA > 0.077 and Model 2: CFI < 0.906; TLI < 0.887; RMSEA > 0.105) in any of the three samples. Including a general factor to these two hypothesized models to produce a bi-factor model also did not yield satisfactory results. Using EFA, we identified four different factor structures in the three samples that were unstable due to cross loadings of the items. When scoring the QLQ-CIPN20 as a simple, additive checklist evidence was found for known groups validity in the first two samples based on Common Toxicity Criteria (CTC-AE), and in the third sample based on exposure to CIPN-inducing chemotherapy.Neither CFA nor EFA yielded support for a stable subscale structure for the QLQ-CIPN20. Scoring the questionnaire as a simple additive checklist results in acceptable validity.

Purpose: To investigate the scale structure and psychometrics of the EORTC chemotherapy-induced peripheral neuropathy module (QLQ-CIPN20). Methods: Using confirmatory factor analyses (CFA), we tested two hypothesized scale structure models of the QLQ-CIPN20 in 473 patients with non-small cell lung cancer, 281 patients with heterogeneous cancer diagnoses, and 500 patients with colorectal cancer. We also modeled the two hypothesized models as bi-factor models. These included a general factor, in addition to the specific domain factors. Additional models were investigated with exploratory factor analysis (EFA). Known groups validity was evaluated where justified. Results: CFA could not confirm the two hypothesized models (Model 1: CFI < 0.926; TLI < 0.914; RMSEA > 0.077 and Model 2: CFI < 0.906; TLI < 0.887; RMSEA > 0.105) in any of the three samples. Including a general factor to these two hypothesized models to produce a bi-factor model also did not yield satisfactory results. Using EFA, we identified four different factor structures in the three samples that were unstable due to cross loadings of the items. When scoring the QLQ-CIPN20 as a simple, additive checklist evidence was found for known groups validity in the first two samples based on Common Toxicity Criteria (CTC-AE), and in the third sample based on exposure to CIPN-inducing chemotherapy. Conclusions: Neither CFA nor EFA yielded support for a stable subscale structure for the QLQ-CIPN20. Scoring the questionnaire as a simple additive checklist results in acceptable validity.

Cerebral amyloid angiopathy (CAA) is pathologically characterized by the progressive deposition of amyloid-Î2 (AÎ2) protein in the walls of small/medium sized arteries and capillaries in the cerebral cortex and overlying leptomeninges, representing an important cause of spontaneous intracerebral haemorrhage and cognitive impairment. Interestingly, a subgroup of CAA patients has been shown to develop vascular inflammation of the affected vessels, associated with vasogenic edema (VE) and to a rapid cognitive decline. This condition, known as CAA-related inflammation (CAA-ri), presents with acute or subacute neurological impairment, behavioral changes, seizures and focal neurological deficits. A definite diagnosis of CAA-ri requires brain and leptomeningeal biopsy that shows perivascular inflammation associated with AÎ2 laden vessels and signs of vasculitis. This distinct syndrome has parallels with what observed in about 5-10% of patients affected by Alzheimerâ€TMs disease (AD) who developed reversible VE after passive immunization with the anti-AÎ2 antibody bapineuzumab, where postmortem examination revealed inflammation and/or vasculitis associated with CAA, implying the discontinuation of the therapeutic protocol. Moreover, recent imaging data on the location of ARIA-E have shown that up to 17% of the treated patients showed signs of VE, even if in the absence of clinical correlates and directly related to the drug dose. Herein, thanks to a novel technique for the ultra sensitive evaluation of anti-AÎ2 (patent application pending), for the first time, we confirmed a direct involvement of these antibodies during the course Pag. of disease in the CSF of 10 CAA-ri, compared to 8 CAA and 20 healthy subjects, demonstrating that the concentration of anti-AÎ2 is specifically increased during the acute phase of the disease. Moreover, we reported a progressive reduction of autoantibodies concentration following steroid treatment, according to clinical-radiological im

The assessment of chemotherapy-induced peripheral neurotoxicity (CIPN) is still uncertain as several of the most frequently used scales do not rely on a formal neurological evaluation and depend on patients' reports and examiners' interpretations. The aim of this study was to compare the assessment of CIPN using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) scale and a formal neurological assessment scored with the Total Neuropathy Score (TNS, i.e., a composite scale designed to grade the impairment in neuropathy patients) to identify possible discrepancies in the diagnosis. In this prospective study, 155 patients treated with cisplatin/carboplatin or with paclitaxel/docetaxel and CIPN were examined in a collaborative oncological/neurological multi-center trial using the NCI-CTC scale and the TNS; the results were then extensively compared. We evidenced that the TNS allows possible misdiagnosed neuropathies to be revealed. In fact, the NCI-CTC evaluation performed by experienced examiners overestimated the occurrence of motor neuropathy, possibly because of the presence of confounding factors (e.g., fatigue, depression, cachexia), which might be difficult to be ruled out without a formal neurological examination. This study strongly indicates that a more formal neurological assessment of patients with CIPN than that achievable with the common toxicity scales (e.g., NCI-CTC) is advisable.

The SCA17 clinical phenotype includes characteristics associated with cerebellar and cortical atrophy such as ataxia, dementia, epilepsy, chorea and parkinsonian features. Here we describe the case of a 38-year-old male presenting with ataxia, cognitive impairment and seizures, who was found to carry 43 repeats on one allele of the TATA-binding protein (TBP) gene. Therefore, genetic analysis of TBP gene triplets was performed on the patient's entire family, identifying three asymptomatic carriers of the same allele. A neuroradiological phenotype appeared to segregate with this allele, suggesting that it may play at least a contributory role in the determination of SCA17.

Chemotherapy-Induced Peripheral Neurotoxicity (CIPN) is a frequent, potentially severe and dose-limiting side-effect of cancer treatment. Despite its clinical relevance that limits the use of several antineoplastic agents and even the future development of new anticancer drugs, several crucial aspects of CIPN remain unsolved, one of which is how to assess its occurrence and severity in the most effective and reliable way. CIPN severity is generally assessed using Common Toxicity Criteria (CTC) scales, although it is well known that significant inter-observer disagreement exists using these scales. Moreover, most CTC scores mix impairment, disability and quality of life measures, which could lead to misinterpretation of the results and unpredictable under- or overestimation of the effect. This uncertainty may lead to different interpretations of the results of the same clinical trials by clinicians and also by regulatory agencies. The use of other types of scale based on clinical and instrumental examinations, or the use of self-administered questionnaires for patients, has not yet really improved the accuracy of CIPN assessment, although some of these tools are promising and deserve to be further validated. As a result, there is a general recognition that CIPN has still not been properly assessed and that improvements should be made. In this review, the available data regarding the different tools used to assess CIPN will be revised and their features will be critically examined, with a special focus on their reliability and reproducibility across examiners and, when available, through direct comparison. © 2009 Elsevier Ltd. All rights reserved.

We investigated a series of bortezomib-treated patients and correlated the course of bortezomib-induced peripheral neurotoxicity with the presence or absence of peripheral neuropathy at baseline. Forty-eight patients were examined with the total neuropathy score reduced version (TNSr), visual analogue score (VAS) for pain, and nerve conduction studies at baseline and after two and four cycles of chemotherapy. Twenty-three patients had a baseline TNSr = 0-2, and 25 patients had a baseline TNSr >2 (median = 6, range 3-13). The course of bortezomib-induced peripheral neurotoxicity was generally more severe in those patients with the highest baseline TNSr. However, among those subjects with a normal baseline TNSr, two patients developed a clinically relevant peripheral neuropathy with a marked increase in TNSr as early as after two cycles of bortezomib treatment (TNSr = 10 and 15, respectively), while after four cycles, three other patients with normal baseline TNSr had a TNSr of 11, 12, and 13. VAS reporting confirmed that painful neuropathy is frequent after bortezomib administration. Our results indicate that the course of bortezomib-induced peripheral neurotoxicity can be severe in subjects with normal neurological examination at baseline, and therefore, careful monitoring during treatment is suggested in these patients.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a major side effect of several antineoplastic drugs. However, despite its clinical importance, there is no agreement as to the best way to assess the severity and changes in CIPN. We have previously demonstrated a correlation between the severity of CIPN, assessed using the Total Neuropathy Score (TNS) or its reduced versions, and several common toxicity scales. In this study, we investigated two series of patients (total number = 173) who were evaluated at baseline and during chemotherapy with the TNS (n = 122) or the TNSc (the TNS version based exclusively on the clinical evaluation of the patients, n = 51) and with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) 2.0, with the aim of comparing the sensitivity to the changes in CIPN severity. In both series, the TNS and the TNSc had a significant correlation with the NCI-CTC in scoring the severity of CIPN, confirming the results of previous studies. Moreover, both the TNS and the TNSc showed a higher sensitivity to CIPN changes. We, therefore, propose the TNSc as a reliable method for assessing not only the severity but also the changes in CIPN.

The experimentally induced neurotoxic effects of paclitaxel and docetaxel have never been compared, since no animal models of docetaxel peripheral neurotoxicity have yet been reported. In this experiment, we examined the effect of the chronic administration of these two taxanes in the Wistar rat using neurophysiological, neuropathological and morphometrical methods. Our results showed that both paclitaxel and docetaxel induced a significant, equally severe and dose-dependent reduction in nerve conduction velocity. On the contrary, the morphometric examination demonstrated that the effect on the nerve fibres was more severe after paclitaxel administration when the same schedule was used. However, the overall severity of the pathological changes was milder than expected on the basis of the neurophysiological results. Our results support the hypothesis that taxanes (and particularly docetaxel) may exert their neurotoxic effect not only on the microtubular system of the peripheral nerves, but also on other less obvious targets. © 2005 Elsevier Ltd. All rights reserved.